Metronomic Vinorelbine and Bevacizumab in Patients With Non Small Cell Lung Cancer

Non Small Cell Lung Cancer Clinical Trial

Official title:

A Phase II Study of the Combination of Metronomic Vinorelbine and Bevacizumab as 2nd Line Treatment in Patients With Non Small Cell Lung Cancer (NSCLC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00755170
• Other study ID #: CT/08.18
• Status: Completed
• Phase: Phase 2
• First received: September 17, 2008
• Last updated: October 3, 2016
• Start date: November 2008
• Est. completion date: October 2016

Study information

• Verified date: October 2016
• Source: Hellenic Oncology Research Group
• Contact: n/a
• Is FDA regulated: No
• Health authority: Greece: National Organization of Medicines
• Study type: Interventional

Clinical Trial Summary

This trial will evaluate the efficacy and safety of metronomic vinorelbine and bevacizumab combination in patients with pretreated, advanced non small cell lung cancer

Description:

Intravenous (IV) vinorelbine is a standard chemotherapy option for the treatment of metastatic NSCLC, either alone or in combination with other agents such as CDDP or Carboplatin with overall response rates (ORR) of 15-35% as 1st line treatment and less than 10% as salvage treatment. For the past few years vinorelbine is available for per os (po) administration with acceptable and reliable pharmacokinetic profiles and with a bioavailability of approximately 40% of the IV dose. In randomized phase II studies IV and po vinorelbine have shown comparable response and overall survival rates. The low dose metronomic chemotherapy that is administered in short intervals has been shown in vitro an in vivo to have antiangiogenic effects. Bevacizumab is a well known anti-angiogenic agent. Recently, a phase III study of 1st line treatment in patients with advanced or metastatic NSCLC showed that the addition of bevacizumab to a platinum-based regimen provided a survival benefit. This study will evaluate the combination of metronomic vinorelbine and bevavizumab as 2nd line treatment of NSCLC.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: October 2016
• Est. primary completion date: October 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically or cytologically confirmed, metastatic (stage IV) non small cell lung cancer

• One previous platinum based chemotherapy regimen with or without taxanes for metastatic NSCLC

• Measurable disease, defined as at least 1 bidimensionally measurable lesion = 20 X 10 mm

• Age = 18 years

• Performance status (WHO) 0-2

• Life expectancy of at least 12 weeks

• Adequate bone marrow (ANC = 1,500/mm3, PLT = 100,000/mm3, Hgb = 11 g/dL), liver (Bilirubin = 1.5 upper normal limit, SGOT/SGPT = 2.5 upper normal limit in the absence of liver metastases or = 5 upper normal limit in the presence of liver metastases), and renal function (Creatinine = 1,5 upper normal limit)

• Patients must be able to understand the nature of this study

• Written informed consent

Exclusion Criteria:

• Second primary malignancy, except for non-melanoma skin cancer. Pregnant or lactating women

• Any serious, uncontrolled comorbidity on the investigator's judgment

• Uncontrolled infection

• Any sustained chronic toxicity > grade 2 according to the NCI CTCAE (version 3.0)

• Brain metastases, except if radiated and asymptomatic

• Radiotherapy within the previous 4 weeks

• Previous radiotherapy to the only measurable lesion

• Proteinuria = 500 mgr of protein daily

• Hemoptysis > 10 cc per event

• Clinically significant hematemesis

• Centrally located lesion or in contact with major vessels

• Pulmonary lesion with cavitation

• Documented hemorrhagic diathesis or coagulation disorder

• Cardiovascular disease (class II-IV NYHA congestive heart failure, myocardial infarction within the previous 4 months, unstable angina, LVEF < normal, ventricular arrhythmia, uncontrolled hypertension)

• Thrombotic event within the previous 6 months

• Concurrent use of aspirin > 325 mgr daily, low molecular weight heparin in therapeutic dose, warfarin or acenocoumarol, non-steroid anti-inflammatory agents

• Concurrent treatment with other anti-cancer drug

• Major surgical procedure within the previous 4 weeks

• Serum ?a+ < 120mg/dL

Study Design

Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer

Intervention

Drug:
• Vinorelbine
Metronomic vinorelbine (p.o) 30 mg total dose/day, every Monday, Wednesday and Friday of each week, continuously without intervals for the equivalence of 6 cycles maximum
• Bevacizumab
Bevacizumab (IV) 10 mgr/Kgr on day 1 and 15 every 4 weeks for 6 cycles maximum followed by Bevacizumab (IV) 10 mgr/Kgr on day 1 and 15 every 4 weeks until disease progression

Locations

Country	Name	City	State
Greece	University General Hospital of Alexandroupolis, Dep of Medical Oncology	Alexandroupolis
Greece	"IASO" General Hospital of Athens, 1st Dep of Medical Oncology	Athens
Greece	"Laikon" General Hospital, Medical Oncology Unit, Propedeutic Dep of Internal Medicine	Athens
Greece	401 Military Hospital of Athens	Athens
Greece	Air Forces Military Hospital of Athens	Athens
Greece	University Hospital of Crete, Dep of Medical Oncology	Heraklion
Greece	State General Hospital of Larissa, Dep of Medical Oncology	Larissa,
Greece	"Theagenion" Anticancer Hospital of Thessaloniki, 2nd Dep of Medical Oncology	Thessaloniki
Greece	Interbalkan Hospital, division of Oncology, Pylaia, Thessaloniki	Thessaloniki

Sponsors (2)

Lead Sponsor	Collaborator
Hellenic Oncology Research Group	University Hospital of Crete

Country where clinical trial is conducted

Greece, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Response rate		Objective responses confirmed by CT or MRI (on 3rd and 6th cycle)	No
Secondary	Toxicity profile		Toxicity assessment on each cycle	Yes
Secondary	Progression free survival		1 year	No
Secondary	Overall survival		1 year	No